Full text of DOI:10.1089/105072503322401087

THYROID
Volume 13, Number 9, 2003
© Mary Ann Liebert, Inc.
Case History
Extramedullary Hemopoiesis in a Thyroid Nodule with
Extensive Bone Metaplasia and Mature Bone Formation
Nikolaos Pontikides,1 Dimitrios Botsios,2 Eleni Kariki,3 Konstantinos Vassiliadis,2
and Gerasimos E. Krassas1
Thyroid nodules may undergo a wide range of degenerative change such as infarction, hemorrhage, or fibro-
sis, which may be localized or extensive and associated with calcification or even ossification. However, the
detection of true bone formation in a thyroid nodule is a very rare occurrence. Extramedullary hemopoiesis
(EMH) has been described in almost every organ of the body, mainly in tissues active in hemopoiesis in em-
bryonic life. It is extremely rare for EMH to occur in the thyroid gland especially in patients without known
chronic anemia. We describe a case of a cold thyroid nodule with histologically proven extensive bone meta-
plasia and formation of mature bone with foci of hemopoietic tissue in a young woman without chronic ane-
mia, which, to the best of our knowledge, is the first to be reported in the English language literature.
Introduction
Case History
OLLOID NODULES OF THE THYROID are usually well cir-
A 34-year-old woman was investigated for a palpable le-
cumscribed and often sharply demarcated from adjacent sion in the thyroid gland. She had a 2-year history of nodu-
C
tissues. They vary in size from approximately 1 mm in di- lar goiter. She reported no compressive symptoms. She had
ameter to several centimeters. Hemorrhage, fibrosis, and no history of previous irradiation to the head or neck, and
cystic changes may be evident. Microscopically chronic in- she was on no medication. She had never smoked. She had
flammation, groups of macrophages, hemosiderin, fibrosis, never had any serious hematologic or other chronic disease
and even calcification or ossification can be found (1). How- in the past.
-
ever, mature bone formation in a thyroid nodule is a rare
On examination she appeared well with a body mass in
occurrence (2,3). Extramedullary hemopoiesis (EMH) has dex of 42 kg/m2, and normal pulse rate and blood pressure
been described in almost every organ of the body, espe- (120/180 mm Hg). Palpation of the neck revealed a hard le-
cially in tissues that were active in hemopoiesis in embry- sion approximately 7 cm in diameter in the right lobe of the
onic life such as the spleen, liver and lymph nodes (4,5). It thyroid gland, with well-defined margins and nodular sur-
is extremely rare, however, for EMH to occur in the thy- face. There was no cervical lymphadenopathy, and no evi-
roid gland. Until now only very few cases of EMH in the dence of tracheal compression or mediastinal syndrome.
thyroid have been described in the English language liter-
Her complete blood count showed a hematocrit of 42.5%,
ature. Two occurred in patients with chronic myelofibrosis hemoglobin level of 14.1 g/L, white blood cell count of 8.4
3
(6,7), and one in a patient with chronic iron deficiency ane- 103 per microliter with normal differential count, and a
mia (8). We describe a case of a cold thyroid nodule with platelet count of 316 103 per microliter. The peripheral
3
histologically proven extensive bone metaplasia and ma- blood smear was normal. Serum iron was 72 g/dL (nor-
m
ture bone formation with foci of hemopoietic tissue in- mal, 50–160) and ferritin 64 ng/mL (normal, 12–161). Her
cluding megakaryocytes and myeloid blasts in a young thyroid hormone levels were also normal. The patient tested
woman without chronic anemia.
negative for thyroid antimicrosomal and antithyroglobulin
1Department of Endocrinology, Diabetes and Metabolism, Panagia General Hospital, Thessaloniki, Greece.
2Fourth Department of Surgery, Aristotle University of Thessaloniki, Greece
3Department of Pathology, G. Papanikolaou General Hospital, Thessaloniki, Greece.
877

878
PONTIKIDES ET AL.
Section from the right lobe—pathologic findings. (1) thyroid follicles; (2) fibrosis with sclerosis; (3) bone forma-
FIG. 1.
tion; (4) intertrabecular spaces filled with mature fat cells.
antibodies. Plain neck and chest radiographs showed mild Pathologic Findings
deviation of the trachea to the left and an osseous appear-
The surgical specimen consisted of the entire thyroid
gland, which weighed 52 g and had brown-tan coloration
ance in the lower right part of the neck, corresponding to the
anatomic site of the palpable thyroid nodule.
Thyroid gland scintigraphy with 6 mCi 99mTc showed in- and nodular surface. The capsule was intact. The right lobe,
creased size of the gland and a cold area in the lower part which was measured 7.5 4.0 3.0 cm, had an extremely
3
3
hard consistency, which made it impossible to obtain sec-
tions before demineralization. The left lobe, which was mea-
of the right lobe. Ultrasound examination revealed increased
volume of the right lobe, with a hyperechogenic solid lesion
measuring 6.8 cm in its maximum diameter. The left lobe
was of normal size with a micronodular architecture. The
sured 2.5 3.0 1.5 cm, had soft micronodular consistency.
3
3
Microscopic examination of the left lobe showed features
trachea was slightly deviated to the left and appeared nor- compatible with a nodular goiter. Thyroid follicles of vari-
mal; no cervical nodes were detected.
able size were separated by fibrous tissue bundles into mul-
tiple nodules. The follicular cells were cuboidal and uniform
without atypia. Sections from the right lobe after decalci-
fication for about 10 days, showed largely the same
Fine-needle aspiration biopsy (FNAB) of the nodule
proved impossible because of the stone-like hardness of the
mass. In view of the size and unusual consistency of the nod-
ule the patient underwent total thyroidectomy under gen- histopathologic features with sclerosis, calcification and ma-
eral anesthesia.
ture bone formation. The inter trabecular spaces were filled
Section from the right lobe—pathologic findings (1) Thyroid follicles; (2) calcification.
FIG. 2.

EXTRAMEDULLARY HEMOPOIESIS
879
Section from the right lobe—pathologic findings. (1) Fibrosis with sclerosis; (2) bone formation; (3) bone marrow
FIG. 3.
spaces; (4) hemopoietic cells; (5) thyroid follicles.
either with mature fat cells or hemopoietic elements includ- both benign and malignant neoplasms of the thyroid gland.
ing a number of megakaryoblasts and blasts of the myeloid However, they occur more frequently in papillary carcino-
series (Figs. 1–4).
mas than in adenomatous follicular nodules (1).
Although calcific deposition may often be detected in a
nodular goiter, maturation of this calcified tissue to mature
bone is extremely rare. A specific osteogenic factor, known
Discussion
Degenerative changes of the thyroid are mostly observed as bone morphogenetic protein (BMP [3]), is essential for ap-
in nodular goiter. Areas of hemorrhage (recent or old), cho- propriate orientation to calcified trabeculae and for forma-
lesterol crystals, deposition bands of fibrous tissue or colloid tion of spaces filled with bone marrow or adipose tissue, as
lakes occasionally filled with fat, may alternate with normal shown in our case.
foci of thyroid tissue. Distinct areas of calcification and even
EMH or myeloid metaplasia is defined as the process of
ossification may also be noted. Rarely, these degenerative blood cell formation in sites other than those that are nor-
changes will reach the stage of calcinosis (1). This last fea- mally active (4). It has been described in cases where there
ture is called metaplastic calcification because it arises on a is increased demand for blood cells after severe and contin-
sclerotic tissue rather than a cartilaginous matrix; it is a fre- uing hemorrhage or hemolysis in newborn or young chil-
quent finding in areas of hemorrhage or sclerosis of any ori- dren (5) and in patients with severe chronic disease of
gin (3,4). Similar degenerative changes can be observed in hemopoietic tissue such as chronic granulocytic leukemia,
Section from the right lobe—pathologic findings. (1) Mature bone marrow with hemopoietic cells; (2) bone for-
FIG. 4.
mation.

880
PONTIKIDES ET AL.
Hodgkin’s disease, primary polycythemia, thalassemia,
sickle cell anemia, pernicious anemia or hereditary sphero-
cytosis (9). It has also been described in chronic iron defi-
ciency anemia (8). Myelofibrosis, however, particularly in the
context of agnogenic myeloid metaplasia, is one of the most
important causes of EMH (10). The most common sites of
EMH are tissues active in hemopoiesis in embryonic life such
as the liver, spleen and lymph nodes (5). However, EMH can
occur in almost every organ and in numerous locations (4).
Development of EMH in the thyroid gland is extremely un-
common and has been described in only three reports (6–8). In
all these cases the diagnosis of EMH was based on FNAB find-
ings, which showed bone marrow elements containing all three
hemopoietic cell lines as in our case. However, two of these
patients had myelofibrosis (6,7) and the third had chronic iron
deficiency anemia with long-term use of methotrexate in the
past for treatment of psoriatic arthritis, which could produce
occult myelodysplasia (8). It should be noted that FNAB may
yield false-positive results in some cases and, for this reason,
an experienced cytolopathologist in this field is required (11).
According to current concepts, EMH foci arise from local
transformation of cells that have hemopoietic potential (4).
Thus, it is believed that in a suitable microenvironment con-
sisting of blood precursor cells, neighboring cells, extracel-
lular matrix, growth factors such as granulocyte-macrophase
colony-stimulating factor, other cytokines and/or hormones,
these pluripotent hemopoietic cells can differentiate into var-
ious cell lines (7). The reactive changes accompanying de-
generative alterations within the nodule (such as inflamma-
tion, necrosis, extensive fibrosis and hypervascularity) may
have played a contributary role for focal EMH (7).
References
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man LE, Untiger RE (eds) Werner & Ingbar’s The Thyroid:
A Fundamental and Clinical Text. Lippincott Williams &
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2. Visona A, Pea M, Bozzola I, Stracca-Pansa V, Meli S 1991
Follicular adenoma of the thyroid gland with extensive en-
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The interesting and extremely unusual finding in our case
was the formation of mature osseous tissue made up of bone
trabeculae containing bone marrow and characteristic he-
mopoietic cells such as megakaryocytes and myeloid blasts.
Megakaryocytes were clearly observed, while the red cell
and granulocyte series, although present, showed degener-
ative changes due to demineralization of the surgical speci-
men. Osteoid was also found in the vicinity of the bony struc-
ture, entrapped in fibrous tissue.
In conclusion, we describe a very rare case of multinodu-
lar goiter with extensive bone metaplasia and mature bone
formation with the presence of foci of hemopoietic tissue
such as megakaryocytes and myeloid blasts in a young fe-
male without any obvious stimulus for EMH.
11. Gay JD, Bjornsson J, Goellner JF 1985 Hematopoietic cells in
a thyroid fine-needle aspirates for cytologic study: Report of
two cases. Mayo Clin Proc 60:123–124.
Address reprint requests to:
G.E. Krassas, M.D.
Department of Endocrinology and Metabolism
PANAGIA General Hospital
N. Plastira 22
N. Krini-Thessaloniki 55132
Greece
krassas@the.forthnet.gr
E-mail: